tbuckley/cabot-search huggingface dataset:
Diagnostic utility of next generation sequencing for somatic variants in cancer: A seven year cumulative cohort.
Authors: Ibrahim Boga, Ozge Sonmezler, Cagla Rencuzogullari, Cem Mujde, Sevcan Tug Bozdogan, Atil Bisgin
Journal: Journal of Clinical Oncology (2023)

e15060 Background: Next generation sequencing (NGS) makes it possible to identify the specific molecular biomarkers to define patient eligibility for targeted therapies via multigene panels. Since then, even though the interpretation of data is complex and not all tumors have genomic alterations within actionable genes, using somatic sequencing for cancer patients becomes a daily routine in clinical oncology. Thus, here we present the data derived from our experience in NGS testing of different cancer patients and biological samples over the course of 7 years in our genetic diagnosis center. Methods: The cohort was consisted of total 5511 cases. While 2590 (46.99%) of them were formalin fixed paraffin embedded (FFPE) tissues, 2906 (52.73%) were liquid biopsies and 15 (0.27%) were other types of biological samples. Total of 15 different cancers were classified (Table 1) and were sequenced using 3 different multigene NGS panels (additional Table 1, BRCAs’ testing for breast/ovarian cancer is not included). NGS was performed via GeneReader NGS System (Qiagen, Germany). Bioinformatics analyzes and variant classification were performed using QCI-Analyze and QCI-Interpret interfaces. Results: As a result, the cases of 93.36% (n = 5145) among all samples were successfully sequenced. The lung cancer group was the most frequent with 47.96% (n = 2643 patients), followed by 491 (%8.9) colorectal 288 (5.23%) and breast cancer patients respectively, while 781 cases (14.17%) grouped as other including many rare cancers. Overall positivity rate was 42.57% (n = 2346) and 366 samples (6.64%) were not sufficient enough to be sequenced. The distribution of positivity rates in relation to cancer type and biological samples used were listed in Table 1. Classification and diagnosis of all tested cases, specimens and Tier 1-2 variants included in this cohort are available on the Additional Table 2. Conclusions: This report is a comprehensive review of the aggregate data across the entire cohort of cancer patients referred to a genetics diagnosis center. While our findings highlight the importance of NGS testing in the somatic setting for cancer patients, also these data stress the importance of diagnosis, biological sample types tested and test results. [Table: see text]
Recurrence rate-based strategy to tailor surveillance scheduling in single hepatocellular carcinoma ≤2 cm after curative therapy: Analysis of 6,105 global patients.
Authors: Qi-Feng Chen, Ning Lyu, Ming Zhao
Journal: Journal of Clinical Oncology (2023)

e16225 Background: For initially diagnosed very early-stage hepatocellular carcinoma (HCC, VEH, i.e. single Hepatocellular Carcinoma ≤2 cm), surveillance after surgical resection (SR) or radiofrequency ablation (RFA) remains largely unclear. We conducted this multicenter study to explore optimal surveillance strategies and evaluate the current surveillance strategies for initially diagnosed VEH after SR/RFA to support the clinical follow-up schedule. Methods: A total of 6,105 initially diagnosed VEH patients who received SR/RFA from global centers were included. After the measurement of the recurrence rate of each month, delayed detection times for tumor recurrence of various follow-up strategies were calculated. The candidate strategies were evaluated according to the delayed detection times and the tumor volume doubling time (TVDT), and a preferable surveillance strategy was recommended. Results: The cumulative 1-, 2-, 3-, 4-, and 5-year recurrence probabilities were 12.7%, 25.9%, 35.7%, 43.7%, and 49.3%, respectively. Based on the monthly recurrence rate, programing surveillance schedules were tailored, which were more effective than current surveillance strategies under the same visits. When patients were followed up every 6 months, the delayed recurrence detection after curative treatment was expected to be 2.35 to 2.57 months. Given that 93.3% of patients did not have &gt;TVDT with a rapid growth subtype when recurrent nodules were detected, a surveillance strategy with a 6-month interval was recommended. Conclusions: Six months of interval surveillance was conservatively supported in patients with VEH after curative therapy.
An individual patient-level meta-analysis of non–small-cell lung cancer leptomeningeal metastases treated with epidermal growth factor receptor inhibitors.
Authors: David Jiahua Bian, Anna-Maria Lazaratos, Sarah M. Maritan, Andrea Quaiattini, Zhimin Zeng, Zhengfei Zhu, Ugur Sener, Rachna Malani, Yu Jung Kim, Eiki Ichihara, Nathaniel Bouganim, Matthew Dankner
Journal: Journal of Clinical Oncology (2023)

e21118 Background: Leptomeningeal metastasis (LM) is a debilitating condition associated with advanced non-small cell lung cancer (NSCLC). When driver mutations in the epidermal growth factor receptor (EGFR) are identified, targeted therapies (TT) represent an appealing therapeutic strategy. However, the efficacy of TT for LM is unknown as LM patients are routinely omitted from clinical trials. Methods: We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of EGFR TT in EGFR-mutant NSCLC LM in accordance with PRISMA guidelines. EGFR-TTs evaluated were erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, zorifertinib, and furmonertinib. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). To assess differences between groups, shared frailty Cox regression models were used to estimate the hazard ratio (HR), 95% confidence interval (CI) and p-value. Results: 7780 abstracts were screened, identifying 126 publications with 232 patients, corresponding to 272 lines of EGFR-TT for NSCLC LM which met inclusion criteria. The overall median PFS (mPFS) in patients receiving any EGFR-TT was 9.15 months and the median overall survival was 14.5 months. In univariable analyses, osimertinib was associated prolonged PFS compared to other EGFR-TT, (mPFS of 11 versus 8 months, HR = 0.64; 95% CI: 0.44-0.93; P = 0.02). Osimertinib was numerically associated with prolonged OS compared to other EGFR-TT (mOS 16.8 months versus 13.6 months, HR = 0.72; 95% CI 0.44-1.17, P = 0.188). In multivariable analyses, ECOG performance status &gt; 2 was independently associated with shortened PFS (mPFS 10 versus 8 months, HR = 1.54, 95% CI: 1.26-3.04; P &lt; 0.05) and OS (mOS 16.5 versus 10 months, HR = 3.33, 95% CI: 1.80-6.18; P &lt; 0.05). Conclusions: In the largest cohort of NSCLC LM treated with EGFR TT compiled to date, osimertinib is associated with marginally improved outcomes compared to other EGFR TTs. ECOG performance status is an independent predictor of prognosis in these patients. These results highlight the need for prospective studies for this difficult to treat patient population.
Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter, single-arm phase 2 trial.
Authors: Wensi Zhao, Liping Li, Junping Huang, Jun Li, Wei Gong, Lilin He, Yuan Chen, Songlin Wang, Xiongjie Yu, Qi Han, Shaobo Ke, Wei Shi, Yongshun Chen
Journal: Journal of Clinical Oncology (2023)

3582 Background: Emerging evidence suggested that chemotherapy in combination with anti-angiogenic targeted agents can achieve higher response in multiple solid tumors. Fruquintinib is a highly selective small-molecule VEGFR inhibitor that has been approved for the third-line treatment in metastatic colorectal cancer (mCRC) patients in China. Here, we assessed the efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in pretreated advanced mCRC patients. Methods: In this prospective, open-label, multicenter, single-arm phase 2 trial (ChiCTR2200059280), patients with mCRC progressed after first-line prior systemic treatment were administered fruquintinib (5~3mg, D1-21, Q4w) and investigator's choice of chemotherapy (fluorouracil ± irinotecan ± oxaliplatin, Q3w) for up to 8 cycles. Patients without disease progression (PD) were followed by fruquintinib maintenance until PD or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety. Results: As the data cutoff on February 10, 2023, 37 patients have been enrolled and treated, with 31 evaluable for efficacy. Median age was 63 years (range, 44-76) and 22 (59.5%) were male. The left colon cancer involved in 28 patients (75.7%). All patients were microsatellite-stable phenotype and 11 (29.7%) had mutations in KRAS gene. 16 (43.2%) patients received prior anti-VEGF therapy. 20 (54.1%) and 11 (29.7%) patients had liver and lung metastases respectively. At a median follow-up of 8.4 months, 28 patients are still on treatment. The ORR is 48.4%, with 15 partial response. The DCR is 90.3%. At data cutoff, median PFS has not yet reached. 23 patients (74.2%) remained progression free at 6 months. In terms of safety, the regimen was well tolerated, mainly grade 1/2 adverse events (AEs). Grade 3/4 AEs were neutropenia (21.6%), leukopenia (10.8%), thrombocytopenia (5.4%), proteinuria, diarrhea, hand-foot syndrome and hypertension accounted for 2.7% respectively. 5 pts received reduced doses of fruquintinib. No treatment-related deaths occurred. Conclusions: Fruquintinib combined with chemotherapy followed by fruquintinib maintenance shows promising efficacy and manageable safety profile for mCRC patients in second-line setting. Updated follow up data will be presented in the future. Clinical trial information: ChiCTR2200059280 .
Pathological analysis of tumor microenvironmental features using deep learning to predict survival of colon carcinomas.
Authors: Frank A. Sinicrope, Garth D. Nelson, Bahar Saberzadeh Ardestani, Dongyao Yan, Kandavel Shanmugam, Steven R Alberts, Qian Shi, Rish Pai, Diana I Segovia
Journal: Journal of Clinical Oncology (2023)

3527 Background: Advances in deep learning may improve the ability to evaluate and quantify pathological features in solid tumors to improve prediction of patient disease-free survival (DFS). We used an artificial intelligence (AI) algorithm to quantify morphological features in the tumor microenvironment of stage III colon cancers. Methods: We analyzed digitized stage III colon carcinomas (N = 402; 382 met QC) from participants in a phase III trial of FOLFOX-based adjuvant chemotherapy that included all available tumors with dMMR and a randomly selected cohort of pMMR tumors (median follow-up 60 months) [NCCTG N0147; Alliance for Clinical Trials in Oncology]. Fifteen morphological features were extracted using the QuantCRC algorithm that segments images into carcinoma (low-grade, high-grade, signet ring cell), stroma (immature, mature, and inflammatory), mucin, tumor/stroma ratio, tumor budding/poorly differentiated clusters (TB/PDC), necrosis, smooth muscle, fat, and tumor-infiltrating lymphocytes (TILs) and tumor area (mucin, epithelium and TB/PDC). Analysis of AI-derived features with clinical variables, molecular alterations ( BRAF/KRAS), and DFS were examined using Kaplan-Meier methodology and multivariable Cox regression. Results: Among the 15 AI-derived morphological features, the following differed significantly between dMMR (n = 191) and pMMR (n = 189) whereby dMMR tumors had lower mature stroma, but higher inflammatory stroma and tumor, higher tumor grade and increased mucin, TB/PDCs, signet ring cells, and TILs (all p&lt; 0.05). Among dMMR tumors, multivariable analysis revealed that tumor area [mucin, epithelium and TB/PDC] (HR adj 0.45, 95%CI (0.24, 0.84), p:0.01, [Q2/3 vs Q1]) and N stage were the only significant and independent prognostic variables. Among pMMR tumors, multivariable analysis identified that tumor budding/poorly differentiated clusters (TB/PDCs) (HR adj 0.20, 95%CI (0.06, 0.61), p:0.01, [Q1 vs Q4]) was the strongest prognostic variable and the only morphological feature that was significantly associated with DFS along with age, N stage and T stage. Conclusions: Using AI, we can extract and quantify distinct morphological features in tumor sections that differ between dMMR and pMMR and multivariately, can significantly and robustly enhance prognostication within each MMR group. Among pMMR tumors, tumor budding/poorly differentiated clusters was the strongest predictor of DFS. Support: NIH U10CA180821, U10CA180882, U24CA196171, R01 CA210509 (to FAS). Study NCCTG N0147 received funds from Sanofi https://acknowledgments.alliancefound.org . ClinicalTrials.gov Identifier: NCT00079274 Key words Artificial Intelligence; Tumor Microenvironment; Colonic Neoplasms; Disease-free survival.
Efficacy and safety of radiation therapy combined with anti-angiogenic agentsand immunotherapy for MSS/pMMR metastatic colorectal cancer: A real-world study.
Authors: Zhenyu Lin, Menglan Zhai, Tao Zhang
Journal: Journal of Clinical Oncology (2023)

e15559 Background: The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) can reshape tumor microenvironment, and their effectiveness has been demonstrated in pattients with microsatellite stable (MSS) or mismatch repair profificient (pMMR) metastatic colorectal cancer (mCRC). Radiotherapy (RT) can induce tumor immunogenic cell death, increase infiltration of tumor-infiltrating T lymphocytes and enhance neoantigen expression. Whether the application of RT can further improve the prognosis of pts with MSS/pMMR mCRC receiving anti-vascular drugs and immunotherapy remains to be explored. Methods: We retrospectively identified data on mCRC pts who received anti-angiogenic targeted agents and ICIs after failure of standard therapy at our institution from January 2015 to September 2022. Pts either received RT (RT+TT+IT group) or did not (TT+IT group) during the course of the disease. Baseline characteristics of the groups were compared with the Chi-squared, Fisher's exact, or the independent sample t-test as appropriate. Progression-free survival (PFS) and overall survival (OS) were examined by the Kaplan-Meier method with a log-rank test. Univariate and multivariate Cox regression analysis was conducted to identify prognostic factors for PFS and OS. Results: Of the 89 pts who received anti-angiogenic targeted therapy in combination with ICIs, 43 (48.3%) received RT and 46 (51.7%) did not. All pts were MSS/pMMR. The objective response rate (ORR) of the RT+TT+IT and TT+IT groups was 18.6% (8/43) and 10.9% (5/46) and the disease control rate (DCR) was 83.7% (36/43) and 67.4% (31/46) (both p &gt; 0.05), respectively. The median PFS time was slightly higher in the RT+TT+IT group than in the TT+IT group (5.0 vs. 4.3 months, p = 0.065). In addition, the PFS of RT sequential/simultaneous TT+IT was superior to TT+IT sequential radiotherapy (RT→IT+TT vs. RT-IT+TT vs. IT+TT→RT: median 7.5 vs. 6.1 v.s 3.8 months, p = 0.004). The median OS of RT+TT+IT group was significantly better than that of TT+IT group (15.2 vs. 7.2 months, p = 0.026). Application of RT appeared to be most benefificial in pts aged 56 or younger, advanced stage of initial diagnosis, metastatic lesions involving ≥2 organs, primary lesion not resected, RAS mutations. Cox multivariate regression analysis showed that the number of anti-angiogenic agents plus ICIs cycles &gt; 4 was an independent prognostic factor for OS. No treatment-related deaths were reported, and radiation pneumonia occurred in one patient in the combined radiotherapy group in a manageable manner. Conclusions: The addition of RT during the course of disease can significantly improve the survival benefit of MSS/pMMR mCRC pts treated with anti-angiogenic drugs combined with ICIs posterior line therapy.
Health care provider and hospital decision-maker perceptions and beliefs on global environmental sustainability in the operating room.
Authors: Emre Gorgun, Sumudu Dehipawala, Matthew O'Hara, Elena Naoumtchik, Gaurav Gangoli, Crystal Ricketts, Giovanni Tommaselli
Journal: Journal of Clinical Oncology (2023)

e18832 Background: Human health is intrinsically linked to the environment’s health; therefore, it is essential for the surgical oncology community, healthcare providers (HCPs) and hospital leadership alike, to incorporate environmentally sustainable practices, while continuing to provide high quality care. Hospital operating rooms (ORs) have a serious environmental impact due to a high rate of greenhouse gas (GHG) emissions, medical waste generation, and energy consumption. An evidence-based understanding of the environmental impact of ORs, as well as sustainability initiatives undertaken to decrease this impact, are crucial for generating and implementing appropriate policies and guidelines. This systematic literature review (SLR) aimed to determine the perceptions and beliefs of HCPs and decision-makers related to environmental sustainability in OR settings globally. Methods: An SLR was conducted following the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines. Embase and PubMed searches were conducted to identify relevant studies published between January 2011 and November 2022. Results: The analysis incorporated thirty-four studies focused on the perceptions and beliefs of OR HCPs and decision-makers on sustainability initiatives. The majority of HCPs across all studies indicated a willingness to engage in these sustainability initiatives such as recycling, while noting frequent barriers that prevent participation, such as lack of awareness and education, hospital funding, facilities to carry out recycling processes, and guidance at the hospital level. One study noted that robotic and laparoscopic procedures, when compared to open procedures, generate greater quantities of waste and GHG emissions. In a survey of 400 anesthesiologists, the lack of support from the hospital and inadequate education were identified as the main barriers to OR recycling by more than 60% of respondents. Common sustainability initiatives suggested by HCPs included creating a sustainability steering committee, reducing overall OR waste via recycling and waste segregation, education and training dedicated to environmental sustainability and enforcement of rules and mandates for sustainability initiatives. Conclusions: HCPs are aware of potential opportunities to make ORs more environmentally sustainable and HCPs are willing, but not necessarily able, to participate in these efforts. Existing literature shows that HCPs have suggestions for how to minimize the environmental impact of the OR. Oncologists interested in adopting more sustainable practices can use this research as a guide for key themes and barriers to acknowledge when designing and implementing their own initiatives. More research is needed on the implementation and impact of sustainability initiatives on the environment.
Determinants of permanent liver limited disease (pLLD) in metastatic colorectal cancer (mCRC).
Authors: Francesc Salva, Cristina Dopazo, René Adam, Hugo Pinto Marques, Darius Mirza, Alessandro Ferrero, Felice Giuliante, Gernot Kaiser, Real Lapointe, Marek Krawczyk, Christophe Laurent, Maximiliano Gelli, Jose Guilherme Tralhao, Santiago Lopez Ben, Irinel Popescu, Helena Isoniemi, Catherine Hubert, Vladimir Evgenievich Zagainov, Axel Andres, Elena Elez
Journal: Journal of Clinical Oncology (2023)

3561 Background: CRC is a complex and heterogeneous disease, with the liver being the most frequent site of metastasis. Around 20% of patients will always progress exclusively in the liver. These patients may be candidates for more aggressive therapeutic procedures that will impact in their outcome. LIVERMET SURVEY Database (LMSD) is a prospective international database, focused on patients operated for CRC liver metastasis, whether resected or not, which purpose is to evaluate patient outcomes and prognostic factors for these resected patients. We propose to analyse all patients enrolled in the (LMSD) to better characterised those determinants that are associated with pLLD. Methods: We analyzed all patients included in the LMSD. Patients with relapse of their disease after the first liver surgery were selected. In order to test associations between hepatic only and extrahepatic metastasis, a univariate and multivariate logistic model was performed with the variables considered clinically more relevant. Imputation of missing data using the mice method (Multivariate Imputation via Chained Equations) was performed. All analyses were performed with R 4.1.1 software. Results: A total of 8715 patients out of 33581 (26%) included in the LMSD presented disease recurrence after a first liver surgery. During their oncological history, pLLD occurred in 1392 patients (16%), and extrahepatic relapse was presented in 7323 patients (84%). The characteristics of patients with pLLD were as follows: 58.4% patients presented synchronic disease, 20.2% had right sided primary tumor, 58.6% presented unilateral disease at time of first hepatic surgery and 20.4% of patients presented R1 surgery. In multivariant analysis, right sided and rectum (HR 0.82. p = 0.001), unilateral liver involvement (HR 0.74, p &lt; 0.001) and &gt; 3cm of diameter in greatest lesion with maximum of 3 lesions (HR 0.85, p = 0.02) were predictive determinants of extrahepatic disease. Only synchronic metastases (HR 1.29, p &lt; 0.001) and male sex (HR 1.15, p = 0.028) were associated with pLLD. Molecular information according to RAS, BRAF and MSI status was not evaluable in a majority of patients since this item has been recently implemented in the questionnaire. Conclusions: This study confirms that about 16% of patients with LLD mCRC will be pLLD mCRC. Despite clinical determinants like synchronic metastatic disease, which is associated with pLLD, further analyses including molecular determinants are needed. Identifying those determinants of pLLD in a scenario where more extreme surgeries and liver transplantations are being considered is a great challenge that needs to be addressed.